Hirschsprung disease (HSCR) is a birth defect with an approximate incidence of 1/5,000 live births, and up to one-third of HSCR patients develop Hirschsprung-associated enterocolitis (HAEC), the leading cause of HSCR-related death. Very little is known about the pathogenesis, prevention, and early diagnosis of HAEC. Here, we used a prospective study to investigate the enteric microbiome composition at the time of surgery as a predictor for developing postoperative HAEC. We identified a microbiome signature containing 21 operational taxonomic units (OTUs) that can potentially predict postoperative HAEC with~85% accuracy. Furthermore, we identified exclusive breastfeeding as a novel protective factor for total HAEC (i.e., preoperative and postoperative HAEC combined). In addition, we discovered that breastfeeding was associated with a lowered risk for HAEC potentially mediated by modulating the gut microbiome composition characterized by a lower abundance of Gram-negative bacteria and lower LPS concentrations. In conclusion, modulating the gut microbiome by encouraging breastfeeding might prevent HAEC progression in HSCR patients.

These results illuminated that FAL1 may work as a ceRNA to modulate AKT1 expression via competitively binding to miR-637 in HSCR, suggesting that it may be clinically valuable as a biomarker of HSCR.

Aim: To discover the potential roles of plasma exosomal miRNAs in Hirschsprung’s disease (HSCR) and identify potential noninvasive biomarkers for early diagnosis of HSCR. Materials & methods: Plasma samples were collected from HSCR patients and matched controls. Exosomes were isolated before high-throughput Illumina sequencing was utilized to gain a profile of dysregulated exosomal miRNAs, followed with further verification in two separate cohorts. Bioinformatics analyses were also adopted to explore the molecular functions of dysregulated miRNAs in Hirschsprung’s disease. Results & conclusion: 31 dysregulated miRNAs were identified with five considered as promising HSCR signatures. Gene enrichment analysis disclosed that the upregulated miRNAs were most likely to participate in ‘extracellular matrix–receptor interaction’ and contribute to HSCR through interfering in cell junctions.